Tumor is one of the tough diseases threatening human health, and presently there are numerous methods for treating tumor. Anti-angiogenesis therapy developed on basis of the relationship between angiogenesis, and tumor growth and metastasis is a promising process, representing a new hope for tumor treatment. As early as 1970s, Folkman proposed that angiogenesis is the biological basis and an important scenario of malignant transformation, growth and metastasis of tumor and that angiogenesis inhibitors could become a new and valuable means to treat tumor. Malignant tumors without angiogenesis tend to be in a semi-dormant state, and are restricted to primary site, grow slowly and thus are unlikely to be too large. Tumors of a size over 2 mm3˜3 mm3 require new blood vessels not only to maintain nutrition supply and excrete metabolites but also to provide favorable channels for their metastasis. With the proliferation of tumor cells, the enlargement of volume of tumor mass, and the change of the microcirculation of tumor mass, tumor cells and host cells are stimulated to produce pro-angiogenesis factors, the production of angiogenesis inhibitor is down-regulated, the balance therebetween in local tissue of tumor is broken, and angiogenesis is initiated, which represents the precondition of rapid proliferation of tumor. Once the new blood vessels formed, the tumor will grow logarithmically, and at the same time massive tumor cells transfer distally by means of the vessels, which have especially adverse effects on the condition and prognosis of patients. It was proved that the 5 years survival rate can be increased notably by using medicament to depress development of tumor and new blood vessels at the edges of tumor.
Based on many years of research on angiogenesis, O'Reilly and Folkman et. al. considered that there must exist pro-angiogenesis factors and angiogenesis inhibitors simultaneously in serums of tumor patients or of animals bearing tumor. These endogenous pro-angiogenesis factors and angiogenesis inhibitors act directly on the vascular endothelial cell in manners such as autocrine, paracrine or the like, influencing their proliferation, migration and formation of tubular structure, and the balance therebetween determines directly the initiation of tumor blood vessels and their developmental orientation, thus being the most important factor regulating tumor blood vessels. Among these, as a part of human endogenous proteins, endogenous inhibitors against tumor angiogenesis play a key role in controlling tumor growth and metastasis, thus represent a good perspective for cancer-resistance. Compared to other anti-tumor medicaments, the endogenous inhibitors against tumor angiogenesis possess many advantages as a medicament: (1) a treatment with the endogenous inhibitors against tumor angiogenesis has good specificity since the angiogenesis has already been initiated when the treatment is performed; (2) have a broad applications because the growth and the metastasis of all kinds of solid tumors depend on the angiogenesis; (3) the medicament can exert directly its effects since vascular endothelial cells expose to blood stream, which allows small dosage and high curative efficacy; (4) gene expressions are relatively stable in the endothelial cells, and it is unlikely to cause a resistance; (5) there is neither resistance caused by repeated administration and nor severe toxic side effect by the cytotoxic medicament. For example, endogenous anti-angiogenesis substances (endostatin) have made a success on the market in China. Many endogenous anti-angiogenesis formulations such as angiostatin and the like have also been in their clinical trials at various stages. Thus it can be seen that they represent a good perspective as candidate for medicament for treating tumors.
However, a long-term administration of the aforementioned endogenous anti-angiogenesis proteins will cause a resistance reaction due to its large molecular weight, low activity, inconvenience of synthesis, and weak immunogenicity for a formulation obtained via purification. In recent years, there is a tremendous development of the researches on endogenous anti-tumor peptide medicaments and derivative peptide medicaments thereof. The endogenous anti-tumor peptide medicaments and derivative peptide medicaments thereof have remarkable advantages over conventional anti-tumor medicaments: as messenger molecules they specifically kill or inhibit tumor cells in different scenarios of the growth and development of tumor cells. Furthermore, the peptides are easy to be synthesized due to their small molecular weight and simple structure, and have established and specific function with high activity, low toxic side effect and no immunogenicity, and thus are safe to be used as a medicament. In recent years, therefore, increasing attentions are drawn to the researches and developments of anti-tumor medicaments with the endogenous peptides and derivative peptides medicaments thereof as subjects.
Thus it can be seen that the endogenous anti-tumor angiogenesis inhibitor peptides have a great potential to be used as a candidate medicament for treating tumor as well as preventing postoperative tumor recurrence and metastasis.